Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of the p53-inducible cyclin-dependent kinase inhibitor p21WAF1/CIP1 in non-neoplastic mucosa, adenoma, and adenocarcinoma of the stomach was examined immunohistochemically and its relationship with p53 expression and proliferative activity was analysed. In normal gastric mucosa as well as in intestinal metaplasia the epithelial cells at the surface which showed no proliferative activity expressed p21WAF1/CIP1, whereas the cells in the deep area of the glands expressing Ki-67 did not. In the neoplastic lesions, the expression of p21WAF1/CIP1 was detected in 78 per cent (112/144) of the adenomas and 76 per cent (262/343) of the adenocarcinomas. The incidence of p21WAF1/CIP1 expression did not differ among histological types of gastric carcinoma. The strong expression of p21WAF1/CIP1 was more frequently observed in carcinomas invading into submucosa or in cases of stages 2, 3, and 4 than in carcinomas limited to the mucosa or in stage 1 cases. The incidence of strongly positive cases was higher in carcinomas with lymph node metastasis than in those without metastasis. There was no apparent correlation between the expression of p21WAF1/CIP1 and the abnormal accumulation of p53 or with proliferative activity measured by Ki-67 expression. These findings overall suggest that p21WAF1/CIP1 might be associated with the senescence of non-neoplastic gastric epithelial cells; that a p53-independent pathway might be substantially involved in the induction of p21WAF1/CIP1 in gastric neoplasia; and that the proliferative activity of gastric cancer might not be solely dependent on control of the cell cycle by p21WAF1/CIP1.
 ...
PMID:Expression of cyclin-dependent kinase inhibitor p21WAF1/CIP1 in non-neoplastic mucosa and neoplasia of the stomach: relationship with p53 status and proliferative activity. 897 68

The tumor suppressor gene p53 has been implicated in the induction of apoptosis in dividing cells. We now show that overexpression of p53 using an adenoviral vector in cultured rat hippocampal pyramidal neurons causes widespread neuronal death with features typical of apoptosis. p53 overexpression did not induce p21, bax, or mdm2 in neurons. X-irradiation of hippocampal neurons induced p53 immunoreactivity and cell death associated with features typical of apoptosis. Overexpression of a constitutively active nonphosphorylatable form of the retinoblastoma gene product blocked x-irradiation-induced neuronal death. However, overexpression of the cyclin-dependent kinase inhibitor p21 did not. Treatment of neurons with transforming growth factor-beta1 protected them from x-irradiation. These results are consistent with a role for p53 in nerve cell death that is distinct from its actions relating to cell cycle arrest.
 ...
PMID:p53 expression induces apoptosis in hippocampal pyramidal neuron cultures. 900 81

CIP1/WAF1, a critical downstream effector of tumor suppressor p53, encodes a cyclin-dependent kinase inhibitor. By Northern blot analysis, the CIP1/WAF1 mRNA level in the tumor was significantly lower than that in the corresponding normal liver from 19 Japanese patients with hepatocellular carcinoma (P < 0.05). In the tumor from only one out of 19 patients (5%), somatic mutations of the CIP1/WAF1 as well as that of p53 gene were identified by RT-PCR/SSCP analysis. These results suggest that the decreased CIP1/WAF1 expression is involved in the carcinogenesis or the progression of hepatocellular carcinoma.
 ...
PMID:Decreased expression and rare somatic mutation of the CIP1/WAF1 gene in human hepatocellular carcinoma. 902 46

Expression of cell cycle regulatory genes in mouse lung was investigated in transgenic models for Clara cell transformation. Clara cells were transformed by generating transgenic mice in which the SV40 large T antigen was expressed under the control of the mouse Clara cell M(r) 10,000 protein promoter. The resulting lung tumors express the large T antigen in normal Clara cells and in tumors, and these tumors express reduced levels of CC10 mRNA. The expression of cell cycle regulatory protein, p53, and the cyclin-dependent kinase inhibitors was analyzed by Northern blot analysis and in situ hybridization throughout the progression of Clara cell transformation in the lung. Increases in specific cyclin-dependent kinase inhibitor steady-state mRNA levels were detected in p15, p18, p27, and p57 during tumor progression. The expression of p15, p57, and p21 mRNAs were verified by in situ hybridization. Using this approach, regulatory genes have been identified that may be involved in the regulation of Clara cell differentiation.
 ...
PMID:Cyclin-dependent kinase inhibitor expression in pulmonary Clara cells transformed with SV40 large T antigen in transgenic mice. 904 Sep 36

Type I interferons (IFN), such as IFN-alpha, are potent antiproliferative and antitumor agents. IFN-tau, originally identified as a pregnancy recognition hormone, is a type I IFN that is related to IFN-alpha. We examine here the mechanism of the antiproliferative effects of IFN-alpha and IFN-tau in terms of their effects on intracellular events that regulate the cell cycle. Both IFN inhibited proliferation of the human Burkitt lymphoma cell line, Daudi, causing accumulation of cells in the G1 phase of the cell cycle. IFN-alpha was more effective than IFN-tau in this regard. Both IFN were found to inhibit the kinase activity of the cyclin-dependent kinase cdk2 in a manner that correlated with their relative abilities to cause cells to accumulate in the G1 phase of the cell cycle. Further, IFN treatment did not affect the expression of cdk2 protein, suggesting that the IFN modulated cdk2 activity through a cdk inhibitor. Consistent with this conclusion, both IFN induced the expression of the cyclin-dependent kinase inhibitor protein p21. The levels of p21 induced also correlated with the relative abilities of the IFN to inhibit cdk2 activity and to arrest cell growth in the G1 phase of the cell cycle. Moreover, following IFN treatment, increased levels of p21 were found complexed with cdk2, consistent with its role in the inhibition of cdk2 activity. These data suggest that p21-mediated inhibition of cdk2 activity plays an important role in the antiproliferative activity of type I IFN. The findings highlight interesting similarities between these cytokines and the products of tumor suppressor genes, such as p53, and may indicate a mechanism for the antitumor effects of the type I IFN.
 ...
PMID:A role for the cyclin-dependent kinase inhibitor p21 in the G1 cell cycle arrest mediated by the type I interferons. 904 66

The tumor suppresser p53 is a cell cycle checkpoint protein that contributes to the preservation of genetic stability by mediating either a G1 arrest or apoptosis in response to DNA damage. p53 causes growth arrest through transcriptional activation of the cyclin-dependent kinase inhibitor p21. During p53-mediated suppression of cell proliferation, p21 is important for coordinating cell cycle progression, DNA replication, and repair of damaged DNA. The purpose of this study is to investigate the expression of p53 and p21 mRNA in association with DNA damage and normal repair in acute immune complex alveolitis in mice. Male ICR mice were injected intravenously with IgG antibodies against oval albumin, aerosolized with oval albumin solution, and killed at 4, 6, 12, 24, and 48 hours and 1 week after aerosolization. We assessed the expression of p53 and p21 mRNA by reverse transcriptase (RT)-PCR and by RT in situ PCR. We also assessed DNA damage by terminal deoxynucleotidyl transferase mediated biotin-dUTP nick-end-labeling (TUNEL) and by gel electrophoresis of DNA extracted from lung tissues. The results of RT-PCR and RT in situ PCR showed that p53 and p21 mRNA were concurrently up-regulated at 4 to 48 hours after aerosolization in alveolar epithelial cells. Bronchial and alveolar epithelial cells were positively stained by TUNEL in this period but not at 1 week after aerosolization or in control mice. The result of electrophoretic analysis of DNA was compatible with that of TUNEL. These studies suggest that the responses of p53 and p21 mRNA are associated with physiologic processes of DNA damage and repair in acute immune complex alveolitis in mice.
 ...
PMID:P53 and p21 (Waf1/Cip1) mRNA expression associated with DNA damage and repair in acute immune complex alveolitis in mice. 904 52

The tumor suppressive effect of p53 is believed to be rooted in its two primary functions: the implementation of cellular growth arrest and the execution of apoptotic cell death. While p53-regulated expression of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1) appears to be central for the implementation of G1 arrest, the participation of p21(Waf1/Cip1) in p53-triggered cell death remains controversial. In the present study, overexpression of p53 in human melanoma SK-MEL-110 cells through use of an adenoviral expression vector (AdCMV.p53) was found to result in apoptosis, while similar infection of primary vascular smooth muscle cells (VSMC) instead resulted in a moderate inhibition of growth. Expression of p21(Waf1/Cip1) was strongly elevated in VSMC, but showed little change in SK-MEL-110 cells, although expression of another p53-regulated gene (GADD45) was comparable in both AdCMV.p53-infected cell types. Evidence that p21(Waf1/Cip1) expression may be required for surviving p53-induced cell death was further supported by the finding that p53 overexpression was highly toxic for p21-deficient mouse embryonal fibroblasts (p21-/- MEFs). In both SK-MEL-110 and p21-/- MEFs, adenovirus-driven ectopic expression of p21(Waf1/Cip1) resulted in a substantial protection against p53-induced apoptosis, indicating that p21(Waf1/Cip1) rescued cells from a path of programmed cell death to one of enhanced survival.
 ...
PMID:p21(Waf1/Cip1) protects against p53-mediated apoptosis of human melanoma cells. 905 Sep 92

Juvenile polyps are regarded as hamartomatous polyps and occur in sporadic and familial syndromic settings. There is increased risk of gastrointestinal neoplasia in patients with juvenile polyposis syndrome, but the molecular mechanisms are not known. We therefore studied 78 colorectal juvenile polyposis from 12 patients with juvenile polyps syndrome and 34 sporadic juvenile polyps for epithelial dysplasia and genetic changes associated with colorectal neoplasia. Dysplasia occurred in 31% of syndromic juvenile polyps but not in sporadic juvenile polyps (P < 0.0001). Topographic control of proliferation and expression of the cyclin-dependent kinase inhibitor p21(WAFI/CIP1) seen in native colorectal epithelium was lost in 79% of dysplastic juvenile polyps and in 8% of nondysplastic juvenile polyps (P < 0.000001). Somatic mutations in the adenomatous polyposis coli (APC) gene were demonstrated in 50% of dysplastic juvenile polyps (3 of 6) but not in any of 16 juvenile polyps without dysplasia (P = 0.01). Both sporadic and syndromic juvenile polyps had K-ras mutations (14%) and there was no relationship to dysplasia. p53 gene product overexpression identified by immunohistochemical staining occurred rarely in dysplastic juvenile polyps (2 of 24, 8%). Our results indicate that the multiple genetic alterations involved in usual colorectal neoplasia also play a role in neoplastic transformation of juvenile polyps, predominantly in juvenile polyposis syndrome.
 ...
PMID:Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps. 906 Aug 32

Mutations of the p53 gene are the most common genetic alteration in malignant human tumors, including ovarian carcinomas of surface epithelial origin. A cyclin-dependent kinase inhibitor, p21waf1/cip1, is thought to be an important mediator of p53-induced cell cycle arrest. Although numerous studies have reported p53 expression and mutation in ovarian tumors, none have correlated p53 expression with that of its downstream effector, p21waf1/cip1. We studied p53 and p21waf1/cip1 expression by immunohistochemistry in 44 ovarian carcinomas of different histologic types and correlated these findings with each other and with proliferation as measured by expression of the Ki-67 nuclear antigen. Fifty percent of tumors expressed p53, whereas 34% expressed p21waf1/cip1. Clear cell carcinomas expressed p21waf1/cip1 significantly more often than other histologic types, and tumors with squamous differentiation showed higher p21waf1/cip1 expression in these areas. There was no correlation of p21waf1/cip1 expression with p53 expression, p53 mutation, or Ki-67 expression. p21waf1/cip1 appears to be induced independently of p53 in these tumors and may be associated with differentiation rather than proliferation.
 ...
PMID:Expression of the p53 induced tumor suppressor p21waf1/cip1 in ovarian carcinomas: correlation with p53 and Ki-67 immunohistochemistry. 910 69

WT1 encodes a zinc finger transcription factor that is expressed in the developing kidney and the inactivation of which leads to Wilms' tumor, a pediatric kidney cancer. We have recently shown that inducible expression of WT1 in osteosarcoma cells triggers programmed cell death, an effect that is associated with transcriptional repression of the endogenous epidermal growth factor receptor. We now show that WT1-mediated apoptosis is preceded by induction of the cyclin-dependent kinase inhibitor p21, associated with G1 phase arrest. This effect is only demonstrated by WT1 isoforms with an intact DNA binding domain, and it is associated with increased expression of endogenous p21 mRNA. WT1-mediated induction of p21 is independent of p53, another tumor suppressor gene known to regulate p21 expression. In the kidney, p21 is expressed in differentiating glomerular podocytes along with WT1. We conclude that induction of p21 expression may contribute to WT1-dependent differentiation pathways in the kidney and potentially to the function of WT1 as a tumor suppressor gene.
 ...
PMID:Induction of p21 by the Wilms' tumor suppressor gene WT1. 910 40


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>